SOLIMASTAT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H32N4O5
Molecular Weight	408.4919
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CO[C@@H]([C@@H](CC(C)C)C(=O)N[C@H](C(=O)NC1=NC=CC=C1)C(C)(C)C)C(=O)NO

InChI

InChIKey=WORSVFBVUCBRIP-VNQPRFMTSA-N

InChI=1S/C20H32N4O5/c1-12(2)11-13(15(29-6)18(26)24-28)17(25)23-16(20(3,4)5)19(27)22-14-9-7-8-10-21-14/h7-10,12-13,15-16,28H,11H2,1-6H3,(H,23,25)(H,24,26)(H,21,22,27)/t13-,15+,16-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C20H32N4O5
Molecular Weight	408.4919
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://adisinsight.springer.com/drugs/800006529 | https://www.ncbi.nlm.nih.gov/pubmed/14970856

British Biotech was developing solimastat [BB 3644], an inhibitor of tumour necrosis factor and matrix metalloproteinase, as a potential treatment for colorectal cancer, inflammatory bowel diseases and rheumatoid arthritis. BB-3644 is an oral, broad-spectrum matrix metalloproteinase inhibitor (MMPI) structurally related to marimastat and BB-94. It is also >10-fold more active than marimastat in inhibiting the processing of cell-bound TNF-alpha. Solimastat development has been discontinued due to significant musculoskeletal toxicity.

Originator

Approval Year

PubMed

Title	Date	PubMed
Ongoing trials with matrix metalloproteinase inhibitors.	2000 Sep	11060801
Metalloproteinase inhibition augments antitumor efficacy of the anti-CD30 immunotoxin Ki-3(scFv)-ETA' against human lymphomas in vivo.	2004 Sep 10	15239135

Sample Use Guides

In Vivo Use Guide

Advanced solid tumours: treatment consisted of twice daily (bd) oral solimastat [BB 3644] for 84 days. The initial dose was 5 mg bd, and subsequent cohorts were treated with 10, 20 and 30 mg bd. In all, 22 patients were enrolled. The dose-limiting toxicity (DLT) was musculoskeletal pain. For 28 days of treatment with BB-3644, 20 mg bd was the maximum tolerated dose (MTD), as at 30 mg bd, six of nine patients developed significant musculoskeletal toxicity by day 28.

Route of Administration: Oral

In Vitro Use Guide

CD30 shedding from the cell line Karpas 299 could effectively be blocked by the hydroxamic acid-based metalloproteinase inhibitor BB-3644 (IC50 = 180 nM)

Substance Class	Chemical Created by `admin` on `Fri Dec 15 17:18:41 GMT 2023` Edited by `admin` on `Fri Dec 15 17:18:41 GMT 2023`
Record UNII	414MEG73VU
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SOLIMASTAT

Official Name

English

solimastat [INN]

Common Name

English

(2S,3R)-3-((1S)-(2,2-DIMETHYL-1-(2-PYRIDYLCARBAMOYL)PROPYL)CARBAMOYL)-2-METHOXY-5-METHYLHEXANOHYDROXAMIC ACID

Systematic Name

English

BB-3644

Code

English

BUTANEDIAMIDE, N1-((1S)-2,2-DIMETHYL-1-((2-PYRIDINYLAMINO)CARBONYL)PROPYL)-N4-HYDROXY-3-METHOXY-2-(2-METHYLPROPYL)-, (2R,3S)-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1970